👤 D A de Luis

The APOA5-1131C allele is related to a worse lipid profile and metabolic response to diet interventions. The present study was designed to investigate the effect of SNP rs662799 on the lipid profile of patients with obesity after a hypocaloric diet with a Mediterranean pattern enriched in ω-6 polyunsaturated fatty acids (PUFA). A population of 362 Caucasian patients with obesity was evaluated. Anthropometric evaluation and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, and adipokines) were measured at basal time and after 12 weeks. All subjects were genotyped rs662799. The APOA5 variant distribution among the 362 patients with obesity was the following: 87.2% (n=316) (TT) were homozygous for the T allele, 12.2% (n=44) (TC) were heterozygous, and 0.6% (n=2) (CC) were homozygous for the C allele. There were only significant differences in triglyceride levels between genotype groups. After 12 weeks of intervention, the following parameters improved in both genotype groups: adiposity parameters, systolic blood pressure, total cholesterol, LDL cholesterol, leptin, adiponectin, and ratio leptin/adiponectin. Insulin levels (delta: -3.5±0.2 UI/L vs. -1.2±0.6 UI/L; p=0.03), HOMA-IR (delta: -1.6±0.1 units vs. -0.3±0.2 units; p=0.01) and triglyceride levels (delta: -18.8±4.1 mg/dl vs. -3.7 ±3.0 mg/dl; p=0.02) decreased in non-C allele carriers. Our data demonstrate that the minor C allele of the APOA5 gene (rs662799) produces a worse response in triglyceride levels, insulin levels, and HOMA-IR after a ω-6 PUFA enriched hypocaloric diet with Mediterranean pattern. Show less

Branched-chain amino acids (BCAA) are essential amino acids playing crucial roles in protein synthesis and brain neurotransmission. Branched-chain ketoacid dehydrogenase (BCKDH), the flux-generating step of BCAA catabolism, is tightly regulated by reversible phosphorylation of its E1α-subunit. BCKDK is the kinase responsible for the phosphorylation-mediated inactivation of BCKDH. In three siblings with severe developmental delays, microcephaly, autism spectrum disorder and epileptic encephalopathy, we identified a new homozygous in-frame deletion (c.999₁₀₀₁delCAC; p.Thr334del) of Show less

This APOA5-1131C allele is related with a higher serum triglyceride levels and perhaps a different metabolic response to a dietary intervention. The aim of the present investigation was to evaluate SNP rs662799 in the A population of 363 Caucasian obese patients was enrolled. Anthropometric parameters and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, adiponectin, resistin, and leptin levels) were measured, at basal time and after 3 months. All patients were genotyped in the rs662799 polymorphism. The C allele carriers of rs662799 of the Show less

This ApoA5-1131C allele of rs662799 variant is related with a higher serum triglyceride levels, and it contributes to increase risk of cardiovascular disease. The aim of the present investigation was to evaluate single nucleotide polymorphism rs662799 in APOA5 gene and its associations with cardiovascular risk factors, MS, and serum adipokine levels. The study involved a population of 1,002 Caucasian obese subjects. Measurements of body weight, waist circumference, fat mass, arterial blood pressure, blood glucose, C-reactive protein, insulin levels, insulin resistance (HOMA-IR), lipid profile, and adipokines levels were recorded. Genotype of ApoA5 gene polymorphism (rs662799) and prevalence of metabolic syndrome (MS) were evaluated. The distribution of the rs662799 polymorphism in this adult population (n = 1,002) was 88.3% (n = 885) (TT), 11.4% (n = 114) (TC), and 0.3% (n = 3) (CC). No significant differences were found between the 2 genotypes in the anthropometric data, MS, or blood pressure. Triglyceride levels were higher in C-allele carriers (delta total group: 19.7 ± 2.1 mg/dL: p = 0.02) than non C-allele carriers. HDL-cholesterol levels were lower in C-allele carriers (delta total group: -6.7 ± 1.1 mg/dL: p = 0.02) than non C-allele carriers. Adiponectin levels were lower in C-allele carriers (delta total group: -11.6 ± 1.0 mg/dL: p = 0.02) too. In C-allele carriers, logistic regression analysis showed an increased risk of hypertriglyceridemia (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2-3.4, p = 0.001) and percentage of low-HDL-C (OR = 2.2, 95% CI = 1.3-3.7, p = 0.002) after adjusting by body mass index and age. C-allele carriers of rs662799 of APOA5 gene showed high rates of low levels of HDL and hypertriglyceridemia, with differences in triglyceride, HDL cholesterol, and adiponectin levels in Caucasian obese subjects. Show less

One SNP in exon 9 (r5883) has been involved with high risk of cardiovascular disease in hypertensive subjects. The goal of the present study was to test the role of this genetic variant on lipid levels and Metabolic Syndrome (MS) in menopausal obese females. The study enrolled a sample of 112 menopausal obese females. Measurements of adiposity parameters, blood pressure, fasting blood glucose, insulin concentration, insulin resistance (HOMA-IR), lipid profile, C reactive protein and prevalence of MS were recorded. Genotype of CETP gene polymorphism (rs5883) was studied. The distribution of the rs5883 polymorphism in this menopausal obese population was 83.9% (n=94) (CC), 15.2% (n=17) (CT) and 0.9% (n=1) (TT). Adiposity parameters, blood pressure, fasting glucose levels, insulin levels, HOMA-IR, C reactive protein, total cholesterol, LDL-cholesterol and triglycerides were similar in both genotype groups (CC vs. CT+TT). Moreover, HDL cholesterol (8.5+1.2 mg/dl; p=0.01) and ratio total cholesterol/HDL-cholesterol (0.5±0.2; p=0.04) were higher in T allele carriers (dominant model). MS percentage was similar in both genotypes (37.6% vs. 27.2%; p=0.43). Logistic regression analysis showed a decreased risk of low-HDL cholesterol in T allele carriers (OR=0.18, 95% CI=0.02-0.77, p=0.03) after adjusting by dietary fatty acid intakes, body mass index and age. The results reported here support that CETP variant rs5883 is related with HDL-cholesterol levels and ratio total cholesterol/HDL-cholesterol. Show less

Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. The purpose of our pilot study was to evaluate the gene expression profiles in the peripheral blood of obese patients without other metabolic complications. A sample of 17 obese patients without metabolic syndrome and 15 non obese control subjects was evaluated in a prospective way. Following 'One-Color Microarray-Based Gene Expression Analysis' protocol Version 5.7 (Agilent p/n 4140-90040), cRNA was hybridized with Whole Human Genome Oligo Microarray Kit (Agilent p/n G2519F-014850) containing 41,000+ unique human genes and transcripts. The average age of the study group was 43.6 ± 19.7 years with a sex distribution of 64.7% females and 35.3% males. No statistical differences were detected with healthy controls 41.9 ± 12.3 years with a sex distribution of 70% females and 30% males. Obese patients showed 1436 genes that were differentially expressed compared to control group. Ingenuity Pathway Analysis showed that these genes participated in 13 different categories related to metabolism and cellular functions. In the gene set of cellular function, the most important genes were C-terminal region of Nel-like molecule 1 protein (NELL1) and Pigment epithelium-derived factor (SPEDF), both genes were over-expressed. In the gene set of metabolism, insulin growth factor type 1 (IGF1), ApoA5 (apolipoprotein subtype 5), Foxo4 (Forkhead transcription factor 4), ADIPOR1 (receptor of adiponectin type 1) and AQP7 (aquaporin channel proteins7) were over expressed. Moreover, PIKFYVE (PtdIns(3) P 5-kinase), and ROCK-2 (rho-kinase II) were under expressed. We showed that PBMCs from obese subjects presented significant changes in gene expression, exhibiting 1436 differentially expressed genes compared to PBMCs from non-obese subjects. Furthermore, our data showed a number of genes involved in relevant processes implicated in metabolism, with genes presenting high fold-change values (up-regulation and down regulation) associated with lipid, carbohydrate and protein metabolism. Show less

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from simple steatosis without inflammation or fibrosis to nonalcoholic steatohepatitis and in the Western countries has become one of the most prevalent chronic liver diseases related to metabolic and lipid alterations. Cholesteryl ester transfer protein (CETP) participates in high density lipoprotein (HDL)-cholesterol metabolism. The aim of our study was to investigate the influence of polymorphism (rs1800777) of CETP gene on liver histological changes, biochemical parameters, and serum adipokines levels in patients with NAFLD. A population of 90 patients with NAFLD was recruited in a cross-sectional study. A biochemical analysis (glucose, c-reactive protein, insulin, homeostasis model assessment-insulin resistance, total cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, triglycerides blood, and adipokines (leptin, adiponectin, and resistin) was realized. Genotype of polymorphism (rs1800777) of CETP gene was studied. Eighty-three patients (92.2%) had the genotype GG (wild type group) and 7 patients (7.8%) had the genotype GA (n = 7) or AA (n = 0; mutant type group). Patients with A allele show significant decrease in liver biochemistry parameters - Alanine amino transferase (delta 10.1 ± 9.9 UI/L; p = 0.01), aspartate aminotransferase activity (delta 13.3 ± 9.5 UI/L; p = 0.02), and gammaglutamine transferase levels (delta 39 ± 30.1 UI/L; p = 0.01). Logistic regression analysis indicated that subjects with A-allele carriers were associated with a decreased risk of lobulillar inflammation (OR 0.18, 95% CI 0.04-0.95, p = 0.04) and a decreased risk of steatosis (OR 0.13, 95% CI 0.02-0.89, p = 0.04). A variant of the polymorphism rs1800777 of CETP gene is independently associated with the presence of steatosis and lobulillar inflammation in subjects with proven biopsy NAFLD. Show less

There is little evidence of the association between CETP SNPs and obesity and/or related metabolic parameters. To analyze the association of the polymorphism rs1800777 of the CETP gene with anthropometric parameters, lipid profile, metabolic syndrome and its components, and adipokine levels in obese subjects without type 2 diabetes mellitus or hypertension. A population of 1005 obese subjects was analyzed. Electrical bioimpedance was performed, and blood pressure, presence of metabolic syndrome, dietary intake, physical activity, and biochemical tests were recorded. Nine hundred and sixty eight patients (96.3%) had the GG genotype, 37 patients the GA genotype (3.7%) (no AA genotype was detected). Fat mass (delta: 4.4±1.1kg; p=0.04), waist circumference (delta: 5.6±2.1cm; p=0.02), and waist to hip ratio (delta: 0.04±0.01cm; p=0.01) were higher in A allele carriers than in non-A allele carriers. HDL cholesterol levels were lower in A allele carriers than in non-A allele carriers (delta: 4.2±1.0mg/dL; p=0.04). In the logistic regression analysis, the GA genotype was associated to an increased risk of central obesity (OR 7.55, 95% CI 1.10-55.70, p=0.02) and low HDL cholesterol levels (OR 2.46, 95% CI 1.23-4.91, p=0.014). The CETP variant at position +82 is associated to lower HDL cholesterol levels, increased fat mass, and central obesity in obese subjects. These results may suggest a potential role of this variant gene in pathophysiology of adipose tissue. Show less

There is few evidence of cholesterol ester transfer protein (CETP) in subjects with obesity and diabetes mellitus. We examined the association of the polymorphism (rs1800777) of CETP gene on anthropometric parameters, lipid profile and adipokines in subjects with obesity and diabetes mellitus type 2. A population of 229 obese subjects with diabetes mellitus type 2 was enrolled. An electrical bioimpedance, blood pressure, dietary intake, exercise and biochemical analyses were recorded. Two hundred and seventeen subjects (94.8%) had genotype GG and 12 GA (5.2%) (genotype AA was not detected). Weight (delta: 14.4 ± 2.1 kg, p = 0.01), body mass index (delta: 2.2 ± 1.1 kg/m2, p = 0.01), fat mass (delta: 11.2 ± 3.1 kg, p = 0.02), waist circumference (delta: 3.9 ± 2.0 cm, p = 0.02), waist to hip ratio (delta: 0.04 ± 0.02 cm; p = 0.01), tryglicerides (delta: 48.6 ± 9.1 mg / dl, p = 0.03) and leptin levels (delta: 58.6 ± 15.9 mg/dl, p = 0.02) were higher in A allele carriers than non A allele carriers. Levels of HDL-cholesterol were lower in A allele carriers than non-carriers (delta: 5.6 ± 1.1 mg/dl, p = 0.03). In regression analysis, HDl cholesterol, weight and fat mass remained in the model with the SNP. Our results show an association of this CETP variant at position +82 on HDL cholesterol, levels and adiposity parameters in obese subjects with diabetes mellitus type 2. Show less

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder affecting several systems caused by a heterozygous deletion in the chromosomal region 7q11.23. A common interval that includes up to 17 genes reported so far is deleted in the great majority of patients. Elastin haploinsufficiency is responsible for the cardiovascular features, but the specific contribution of other deleted genes to the WBS phenotype remains unknown. We have fully characterised a gene commonly deleted in WBS, WBSCR14, previously reported in a truncated form as WS-bHLH. The WBSCR14 cDNA encodes an 852amino acid protein with a basic helix-loop-helix-leucine-zipper motif (bHLHZip) and a bipartite nuclear localisation signal (BNLS), suggesting a function as a transcription factor. WBSCR14 is expressed as a 4.2kb transcript predominantly in adult liver and at late stages of foetal development. The WBSCR14 locus encompasses 33 kb of genomic DNA with 17 exons. Two intragenic polymorphic dinucleotide repeats have been identified and used to verify hemizygosity in WBS patients. We have also cloned the mouse ortholog and mapped its locus to mouse chromosome 5, in a region of conserved synteny with human 7q11.23. Given that other bHLHZip proteins are dosage sensitive and based on the putative function of WBSCR14 as a transcription factor, hemizygosity at this locus could be involved in some features of WBS. Show less